In present post-genome research, attempts have been made to discover drugs based on protein's three-dimensional structure; therefore, there is an urgent need for protein structure analysis. An optimal technique for protein structure analysis is crystal structure analysis. However, protein crystallization, an essential step of crystal structure analysis, is currently very difficult because the success rate is low, a considerable amount of time is required, etc. For this reason, protein crystallization is a hindrance in the three-dimensional structure analysis of proteins, and for drug discoveries utilizing them.
Generally, in order to precipitate a protein crystal from a protein-containing solution, the degree of supersaturation must be made high by means of either a solvent vaporization, a temperature change, or a precipitant. When the degree of supersaturation is low, nucleation may not occur, nucleation and crystal growth may be delayed, etc. Conversely, when the degree of supersaturation is too high, crystals are abruptly precipitated and undergo rapid growth, causing quality defects in the obtained crystals; further, an amorphous precipitate separated from the solution is likely to be produced. Usually, the crystallization conditions are determined as a result of trial and error by actually making several to a great number of attempts at crystallization; however, this requires a great deal of labor and time, and is thus inefficient.
In order to solve the above problems, a method for producing crystals within a short period of time by irradiating a protein-containing solution with a short-pulse laser so as to force the nuclei of crystals to generate, then stirring the solution, has been developed (see Non-Patent Document 1, Patent Document 1, etc.). Additionally, as a method suitable for growing high-quality large-sized protein crystals, a method comprising growing a crystal on the interfaces of two liquids upon decrease of the temperature has been proposed (see Non-Patent Document 2, etc.).
On the other hand, reagent kits for screening protein crystallization conditions, which utilize the crystallization-accelerating properties of certain precipitants and buffers (for example, products from Hampton Research Corp., Emerald BioStructures, Inc., Jena Bioscience GmbH, Molecular Dimensions Ltd., etc.), are commercially available. There is no clear theory about protein crystallization. A technique generally utilized therefor is to first find crystallization conditions by carrying out a screening under a wide range of conditions (an initial screening or a random screening), and subsequently narrowing the obtained crystallization conditions down to the optimal crystallization conditions (the elaboration of conditions). Therefore, according to the above process, it can be said that success of crystallization of a target protein relies on whether crystallization conditions can be found during the initial screening. Further, in order to crystallize a target protein, the target protein must have high purity suitable for crystallization.
The above-mentioned commercially available reagent kits for screening crystallization conditions are useful because it can be easily utilized. However, the reagent kits do not always obtain crystals in high probability; therefore, the development of a screening reagent that can precipitate protein crystals in higher probability is anticipated. There is also a demand for a reagent that makes the crystallization of proteins with low purity possible.    Patent Document 1: WO 2004/018744    Non-Patent Document 1: Journal of the Japanese Association of Crystal Growth, Vol. 29, No. 5, 2002    Non-Patent Document 2: Journal of the Japanese Association of Crystal Growth, Vol. 29, No. 3, 2002